3—取代—4—氧—3H—咪唑并[5,1—d][1,2,3,5]四嗪—8—羧酸衍生物的合成及其抗癌活性研究

根据咪唑四嗪酮类抗癌药物构效关系研究结果，以替莫唑胺和米托唑胺为先导化合物，设计合成了10个3－取代－4－氧－3H－咪唑并5,1-d]1,2,3,5]四嗪－8－羧酸及其衍生物，以4－氨基咪唑－5－甲酰胺盐酸盐为起始原料，经酰化，重氮化环合得到咪唑四嗪酮环，再经3位和8位官能团转化，得到目标化合物，其中5个目标化合物未见文献报道，其结构均经红外光谱，核磁共振氢谱和元素分析等数据证实，经体外抗癌活性筛选，3个化合物表现出良好的抗癌活性。

Synthesis and Antitumour Activities of 3-Substituted 4-Oxo-3H-imidazo[5,1-d][1,2,3,5] tetrazine-8-carboxylic Acids and Their Derivatives

Based on the antitumour mechanism of temozolomide and the SAR study result of imidazotetrazinone antitumour drugs,3-substituted 4-oxo-3H-imidazotetrazine- 8-carboxylic acids and their derivatives were designed and synthesized.Nitrosation cyclisation of 5-amino-1-carbamoylimidazole-4-carboxamides afforded 3-substituted 4-oxo-3H-imidazo tetrazine-8-carboxamide.The facile conversion of 3- or 8- functional groups gave other imidazotetrazinones.Of the ten target compounds,five were novel compounds,of which the chemical structures were characterized by the applications of elemental analysis,IR, 1H-NMR, 13 C-NMR and MS.The chemical entities were tested against GM 892A cell (Mer -) and Raji cell (Mer ) and three compounds had significant antitumour activities.